Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper--a review.
Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper--a review.
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DOI：
10.1177/1534735402238185
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发表时间：
2002-12-01
影响因子：
2.9
通讯作者：
Merajver, Sofia D
中科院分区：
文献类型：
--
作者：
Brewer, George J;Merajver, Sofia D
四硫钼酸盐(TM)是一种治疗肝豆状核变性的新药，是一种很有前途的抗血管生成药物。由TM降低到抗血管生成窗口的铜水平已在各种动物模型和患者中显示出抗癌效果。到目前为止，唯一严重的毒性是过度治疗和过度的骨髓铜消耗。由此产生的贫血和/或白细胞减少症很容易通过减少剂量或停药治疗。TM作为抗癌剂功效的基本概念是，当人体的铜状态处于窗口时，细胞对铜的需求得到满足，毒性被避免。通过跟踪血清铜蓝蛋白可以相对容易地监测铜的状况，铜蓝蛋白是一种由肝脏分泌的含铜蛋白质，其分泌速度取决于肝脏中可结合到蛋白质中的铜量。作者推测，铜水平是一种原始的血管生成和生长信号调节因子，在整个进化过程中一直保持不变。
A new anticopper drug, tetrathiomolybdate (TM), developed for Wilson's disease, is a very promising antiangiogenic agent. Copper levels lowered into an antiangiogenic window by TM have shown efficacy against cancer in a variety of animal models as well as in patients. The only significant toxicity so far results from overtreatment and excessive bone marrow depletion of copper. The resulting anemia and/or leukopenia is easily treatable by dose reduction or drug holiday. The underlying concept for TM efficacy as an anticancer agent is that when the body's copper status is in the window, cellular copper needs are met and toxicity is avoided. Copper status is relatively easily monitored by following serum ceruloplasmin, a copper-containing protein secreted by the liver at a rate dependent upon the amount of copper in the liver available to incorporate into the protein. The authors speculate that the copper level is a primitive angiogenesis and growth-signaling regulator that has been retained throughout evolution.